Cultures of normal cells are relatively inensitive to heat, while malignant cells in culture are highly sensitive to therma treatment. It is proposed that quantitative cellular radiobiological studies be carried out to determine wheter the therapeutic ratio can be increased by exploiting a differential thermal sensitivity between normal and malignant cells in culture. Both plateau and log phase cultures of HeLa cells will be used to simulate the behavior of in vivo solid tumors, while 3T3 cells and WI-38 cells, highly density dependent cultures will be used as experimental models of normal tissue. Dose survival curves will be obtained following irradiation of plateau or log phase cultures with or without post-irradiation thermal treatment. Further studies with mitoticaly synchronized cells will be carried out to elucidate cellular mechanisms of termal enhancement of radiosensitivity. Differential thermal enhancement of the radiosensitivity of normal and malignant cells suggests that improved control of irradiated tumors could be obtained by heating them. The present study will help establiss an optimal-time-dose fractionation scheme for combined radiation and heat treatment.